The cultures weren't gone. There were still mound building cultures active in the South when Spaniards arrived. Disease most likely played a large factor but to

The cultures weren't gone. There were still mound building cultures active in the South when Spaniards arrived. Disease most likely played a large factor but to a certain extent it is a mystery. The American policies ensured that there cultures were nearly wiped from the planet. There was no chance for a rebound of population because of the constant disruption due to displacement and forced migration. This is without the warfare which wasn't the primary source of devastation although it was quite brutal at times. There were a large number of promises of land that were never honored. Look at the Wyandotte's removal from Ohio, they were promised 175,000 acres of land in the West but received nothing of the sort once they gave up their last remaining homestead. They had to find a spot to stay with a fellow tribe. This is all documented and the removal of the American Indian was and remains a real injustice and the impacts are still being felt.